1. LIVER Liver functions Bile pigment metabolism
Degradation of hemoglobin
Disorders of bile pigment metabolism
Liver diagnostic enzymes

2. Liver functions
Liver performs many important functions dealing with or affecting metabolism, excretion of various substance, protection, circulation and blood coagulation.
Metabolic functions:
- Carbohydrate metabolism (glycogenesis from
glucose and stored in liver, glycogenolysis).
Protein synthesis (almost all of the plasma
proteins are synthesized in the liver), lipoproteins
blood coagulation factors: V, VII, X and IX.

3. - Lipid metabolism: plasma lipoproteins,
cholesterol, phospholipids, and triglycerides.
Other synthesis or transformations: conversion of
keto acid to amino acid, production of ketone
bodies(acetoacetic acid and β–hydroxybutyric
acid) from acetyl-CoA, a.a from glucose, lactate
to glucose, synthesis fatty acids from acetyl-CoA.
Storage functions: liver is the primary storage site
for glycogen, vitamins A, D, and B12 , iron.
Excretory functions: liver excretes bile (bilirubin),
bile salts (cholic acid), some dyes, heavy metals,
enzymes and many waste products.

4. Protective functions: liver protects the body
from foreign and dangerous materials by
- Phagocytic action. Liver contains many
phagocytic cells called Kupffer cells (remove
foreign materials from blood.
- Detoxification: involve esterification,
methylation, oxidation, reduction. Ammonia is
converted to urea.
Circulatory functions: liver play a role in
immunologic defense, helps to regulate blood
volume.

5. Bile pigment metabolism
Bilirubin
Bilirubin is the principal pigment in the bile.
It is derived from breakdown of hemoglobin.
RBC lives only 120 days.
The destruction of old RBC occur in reticuloendothelial (RE) system by phagocyte cells.
That destroy are located in spleen, liver and bone marrow.

6. Degradation of hemoglobin
1- Splitting off of protein globin, which hydrolyzed to a.a. The porphyrin ring of heme molecule is broken open. The resulting open chain of tetrapyrrol loses its iron. The resulting pigment is reduced to form bilirubin, reddish yellow waste product that must be excreted.

7. 2- Bilirubin leaves the reticuloendothelial cell and bonds to plasma albumin.
3- Bilirubin-albumin transferred into liver cells by active process then bilirubin is detached from albumin.
4- Esterification (conjugation) of bilirubin to bilirubin diglucuronide (BDG) by the of enzyme glucuronyl-bilirubin transferase.
5- BDG (conjugated bilirubin) is water soluble and secreted from the liver.
6- BDG , with the rest of bile passes into bile duct. Bile is produced continuously by liver.
7- BDG reaches the colon and exposed to the action of bacteria whose enzymes cleave off BDG into urobilinogen.

8. 8- A portion of urobilinogen is absorbed into liver and re-excreted it into the bile. Small portion of urobilinogen reaches the peripheral circulation and excreted by kidney.
9- Urobilinogen in colon is partially oxidized to urobilin and other brownish pigments that are excreted in the feces

9. Disorders of bile pigment metabolism
A bout mg of bilirubin are produced daily in normal healthy adult.
Normal concentration of total bilirubin in serum ranges from mg/dl.
Normal concentration of esterified bilirubin (conjugated)(direct) in serum may be up to 0.3mg/dl.
When the bilirubin concentration in blood rises, the pigment begins to be deposited in sclera of the eye and in the skin. This yellowish pigmentation in the skin or sclera is known as jaundice.

10. Disorders of bile pigment metabolism
Most liver diseases and several nonhepatic disorders are companied by jaundice.
A excessive load of bilirubin (hemolytic diseases , chronic hemolytic anemia)
Defective transport into the hepatocyte. This transport defect is known as Gilberts disease.
Impairment in esterification of bilirubin A) physiologic jaundice of new born due to the UDPG transferase enzyme is not fully developed. B)Hemolytic disease of new born due to Rh and ABO system incompatibility.
Congenital deficiency of UDPG transferase. Known as the Crigler-Najjar syndrome .

11. Disorders of bile pigment metabolism
5) Disturbances in excretion of bilirubin. (Cholestasis), hyperbilirubinemia. 6) Intrahepatic . Viral hepatitis, hepatitis produced by toxic (drug, chemicals like phosphorus, organic arsenicals, carbon tetrachloride and chloroform), cirrhosis, hepatic edema. 7) Posthepatic. These include all type of extrahepatic cholestasis or obstruction of the flow of bile into intestine, may due to stones in the bile ducts or gallbladder, by carcinoma of the head of pancreas, by other tumors.

13. Liver diagnostic enzymes
Number of enzymes are helpful in diagnosis of liver function they are called diagnostic enzymes.
Alkaline phosphatase (ALP). The enzyme distributed in many tissues including osteoblasts, cells lining the sinusoids and bile canaliculi . Normal range 2o-1o5u/L. The increase in ALP activity is due to liver lesion such as, carcinoma, amebic abscess, amyloidosis, granulomatous lesion(sarcoidosis, tuberculosis of liver)

14. Liver diagnostic enzymes
2. Aspartate aminotransferase (AST) (GOT). 3. Alanine aminotransferase (ALT) (GPT). The liver is a rich source of both enzymes GOT and GPT, Normal range : GOT male up to 37u/L female up to 31u/L GPT male up to 40u/L